Objective. To observe the effects of resveratrol (Res) on the antioxidative function and estrogen level in an Alzheimer’s disease (AD) mouse model. Methods. First, we examined the effects of Res on an AD mice model. SAMP8 mice were selected as the model, and normal-aging SAMR1 mice were used as the control group. The model mice were randomly divided into three groups: a model group, high-dose Res group (40mg/kg, intraperitoneal (ip)), and low-dose Res group (20mg/kg, ip). After receiving medication for 15 days, the mice were subjected to the water maze test to assess their spatial discrimination. The spectrophotometric method was used to detect the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) as well as the malondialdehyde (MDA) content. Quantitative PCR (q-PCR) was used to detect SOD, GSH-Px, CAT, and heme oxygenase-1 (HO-1) mRNA level changes. Western blot analysis detected HO-1 and Nrf2 protein expression. Second, we researched the effect of Res on the estrogen level in the SAMP8 model mice. The model mice were randomly divided into four groups: a model group, estrogen replacement group (0.28 mg/kg, intramuscular (im), estradiol benzoate), high-dose Res group (5 mg/kg, im), and low-dose Res group (2.5 mg/kg, im). The mice were injected, once every three days, for 5 weeks. Q-PCR was used to detect brain tissue mRNA expression changes. Western blot analysis detected ERα, ERβ, and ChAT protein expression. An enzyme-linked immunosorbent assay (ELISA) kit was used to detect the expression of E2 and amyloid β protein (Aβ) in brain tissue. Results. Compared with the control treatment, Res could improve the spatial abilities of the mice to a certain extent and also increase the expression of SOD, GSH-Px, CAT, and HO-1 at the mRNA level (P<0.05). In addition, enhanced SOD, GSH-Px, and CAT activities and HO-1 protein levels and decreased MDA content (P<0.05) were detected in the brain tissue of the Res-treated mice. The cytoplasmic Nrf2 content in the Res-treated mice was also decreased while the nuclear Nrf2 content and the nuclear translation rate of Nrf2 were increased (P<0.05). Res could decrease the expression of ERβ in the brain tissue at the mRNA and protein levels and the expression of Aβ in the brain tissue at the protein level. Res could also increase the mRNA and protein expression of ERα and ChAT and the protein expression of estradiol in the brain tissue. Conclusion. Res can increase the antioxidant capacity of AD models through the Nrf2/HO-1 signaling pathway. In addition, Res can enhance estrogen levels in an AD model. These findings provide a new idea for the treatment of AD.

Background: Many prospective cohort studies have investigated the association between nut consumption and risk of coronary artery disease (CAD), strok

MicroRNAs (miRNAs) are small noncoding RNAs that modulate the cellular transcriptome at the post-transcriptional level. miRNA plays important roles in different disease manifestation, including type 2 diabetes mellitus (T2DM). Many studies have characterized the changes of miRNAs in T2DM, a complex systematic disease; however, few studies have integrated these findings and explored the functional effects of the dysregulated miRNAs identified. To investigate the involvement of miRNAs in T2DM, we obtained and analyzed all relevant studies published prior to 18 October 2016 from various literature databases. From 59 independent studies that met the inclusion criteria, we identified 158 dysregulated miRNAs in seven different major sample types. To understand the functional impact of these deregulated miRNAs, we performed targets prediction and pathway enrichment analysis. Results from our analysis suggested that the altered miRNAs are involved in the core processes associated with T2DM, such as carbohydrate and lipid metabolisms, insulin signaling pathway and the adipocytokine signaling pathway. This systematic survey of dysregulated miRNAs provides molecular insights on the effect of deregulated miRNAs in different tissues during the development of diabetes. Some of these miRNAs and their mRNA targets may have diagnostic and/or therapeutic utilities in T2DM.

Background: Inflammation and obesity have been widely recognized to play a key role in Diabetes mellitus (DM), and there exists a complex interplay between them. We aimed to clarify the relationship between inflammation and DM, as well as the mediating role of obesity in the relationship.Methods: Based on the National Health and Nutrition Examination Survey (NHANES) 2005–2018. Univariate analyses of continuous and categorical variables were performed using t-test, linear regression, and χ2 test, respectively. Logistic regression was used to analyze the relationship between Systemic Immune-Inflammatory Index (SII) or natural logarithm (Ln)-SII and DM in three different models. Mediation analysis was used to determine whether four obesity indicators, including body mass index (BMI), waist circumference (WC), visceral adiposity index (VAI) and lipid accumulation product index (LAP), mediated the relationship between SII and DM.Results: A total of 9,301 participants were included, and the levels of SII and obesity indicators (BMI, WC, LAP, and VAI) were higher in individuals with DM (p < 0.001). In all three models, SII and Ln-SII demonstrated a positive correlation with the risk of DM and a significant dose–response relationship was found (p-trend <0.05). Furthermore, BMI and WC were associated with SII and the risk of DM in all three models (p < 0.001). Mediation analysis showed that BMI and WC mediated the relationship between SII with DM, as well as Ln-SII and DM, with respective mediation proportions of 9.34% and 12.14% for SII and 10.23% and 13.67% for Ln-SII (p < 0.001).Conclusion: Our findings suggest that increased SII levels were associated with a higher risk of DM, and BMI and WC played a critical mediating role in the relationship between SII and DM.

SIRT1 has many important molecular functions in aging, and the estrogen receptors (ERs) have a vasculoprotective effect, although the detailed mechanism for the roles of SIRT1 and ERs in vascular aging remains unclear. We found that ERβ expression in the endothelium was reduced in aging mice, and the expression of ERα and SIRT1 did not change, while SIRT1 activity declined. Further investigation showed that the ERβ expression was regulated by SIRT1 through complexes of SIRT1-PPARγ/RXR-p300 that bind to a PPRE (PPAR response element) site on the ERβ promoter, and the declined SIRT1 function in aging mice was due to compromised phosphorylation at S154. A single-mutant SIRT1-C152(D) restored the reduced ERβ expression in the endothelium with minimized reactive oxygen species generation and DNA damage and increased mitochondrial function and fatty acid metabolism. In high-fat diet aging mice, the endothelium-specific delivery of ERβ or SIRT1-C152(D) on the vascular wall reduced the circulating lipids with ameliorated vascular damage, including the restored vessel tension and blood pressure. We conclude that SIRT1-mediated ERβ suppression in the endothelium contributes to vascular aging, and the modulation of SIRT1 phosphorylation through a single-mutant SIRT1-C152(D) restores this effect.